ArticlePloS one2015
Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- The Simultaneous Deletion of pH-Sensing Receptors GPR4 and OGR1 (GPR68) Ameliorates Colitis with Additive Effects on Multiple Parameters of Inflammation.International journal of molecular sciences · 2025Article
- The GPR4 antagonist NE-52-QQ57 increases survival, mitigates the hyperinflammatory response and reduces viral load in SARS-CoV-2-infected K18-hACE2 transgenic mice.Frontiers in pharmacology · 2025Article
- Review
- Molecular basis of proton-sensing by G protein-coupled receptors.bioRxiv : the preprint server for biology · 2024Article
- Proton Sensing GPCR's: The missing link to Warburg's Oncogenic Legacy?Journal of cancer biology · 2024Article
- Article
- Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.Frontiers in physiology · 2023Review
- The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model.Scientific reports · 2020Article
- Crystal structure, Hirshfeld surface analysis and DFT studies of 6-bromo-3-(12-bromo-dodec-yl)-2-(4-nitro-phen-yl)-4Acta crystallographica. Section E, Crystallographic communications · 2020Article
- Involvement of GPR4 in increased growth hormone and prolactin expressions by extracellular acidification in MtT/S cells.The Journal of reproduction and development · 2020Article
- The Proton-Sensing GPR4 Receptor Regulates Paracellular Gap Formation and Permeability of Vascular Endothelial Cells.iScience · 2020Article
- Can GPR4 Be a Potential Therapeutic Target for COVID-19?Frontiers in medicine · 2020Article
- Review
- Increased luminescence of the GloSensor cAMP assay in LβT2 cells does not correlate with cAMP accumulation under low pH conditions.The Journal of reproduction and development · 2019Article
- Pharmacological inhibition of GPR4 remediates intestinal inflammation in a mouse colitis model.European journal of pharmacology · 2019Article
- BClACS omega · 2019Article
- GPR4 deficiency alleviates intestinal inflammation in a mouse model of acute experimental colitis.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells.International journal of molecular sciences · 2017Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.
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